Biopsy not required for Idiopathic Pulmonary Fibrosis Dr. Altay Sahin Hacettepe University

1
Biopsy not required for Idiopathic Pulmonary
FibrosisDr. Altay Sahin Hacettepe University
2

• IPF is an idiopathic interstitial pneumonitis,
  which has the histological presentation of UIP
  and leads to chronic fibrosis
• UIP pattern is not specific for IPF, can be also
  found in Collagen Vascular Disease (CVD) and even
  sarcoidosis
• Major criteira for the diagnosis A) the other
  causes for ILD should be excluded, B) PFT defect,
  inadequate gas exchange, C) consistent HRCT
  findings, D) BALF analysis not supporting an
  alternative diagnosis, a) Age gt50 years, b) acute
  emergence of dyspnea, c) duration of disease gt3
  months, d) Bibasillar inspiratuar crackles

3
Gregory B. Diette John C. Scatarige Edward F.
Haponik Barry Merriman Elli.. Do
High-Resolution CT Findings of Usual Interstitial
Pneumonitis Obviate Lung....Respiration Mar/Apr
2005 72, 2134-141

• Experienced with the help of HRCT and clinical
  presentation radiologist can diagnose IPF, LAM,
  Eosinophilic granuloma, sarcoidosis and PCP with
  a high rate of correct result.
• Biopsy from different lobes may show different
  histopathology upto 26 of cases
• Most of the clinicians in US accept HRCT in the
  diagnosis of IPF, Asbestosis, Silicosis, ve
  bronchiectasis. Only 3 does not accept HRCT
  instead of biopsy.
• Only 60 of the clinicans have read ATS/ERS
  guide, 10 were aware, while the others were
  unaware

4
Fishbein MC. Chest 2005128(5)520S-525S
Peckham RM, et al. Respiration 200471165-169

• Board certified specialists evaluated the
  clinical and HRCT findings in 26 patients
  undergoing surgery and put the diagnosis of UIP
  in 14, NSIP in 5, sarcoidosis in 2, malignancy in
  2, COP in 2, respiratory bronchiolitis associated
  ILD and end stage fibrosis
• For the diagnosis of IPF Sensitivity was 71,
  positive predictive value was 77, spesifity was
  75, negative predictive value was 69,
• there was 4 false negative and 3 false positive
  cases

5
Kappa - Agreement

• gt0.8 almost perfect agreement
• 0.6-0.8 substantial agreement
• 0.4-0.6 moderate agreement
• 0.2-0.4 fair agreement
• 0.0-0.2 slight agreement
• lt0.0 poor agreement

6
Nicholson AG, et al. Interobserver variation
between pathologist in diffuse parenchymal lung
disease. Thorax 200459500-505

• Mean kappa for the first choice diagnosis was
  0.38, and improved to 0.43 when the biopsies were
  received from multiple lobes
• Weighted kappa, which shows the diagnostic
  probability had a mean of 0.58 with a range of
  0.40-0.75
• Confidence in diagnosis was low in 18 of the
  biopsies
• Difference between the pathologists in the
  diagnosis of NSIP especially the differential
  diagnosis from IPF exceeded 50

7
Irish Thoracic Society in collaboration with the
Thoracic Society of Australia and New Zealand and
the Group, a subgroup of the British Thoracic
Society Standards of Care Committee, A U Wells, N
Hirani and on behalf of the BTS Interstitial Lung
Disease Guideline Interstitial lung disease
guideline Thorax 200863v1-v58

• In the UK histopathological panel, primary
  diagnosis proportion was too low to be for the
  clinical use. For the majority of the cases
  histopathological features were indistinct, and
  consistent with two or more of the diagnoses.
• Another important problem was that the biopsy was
  not representative of the predominant disease.
  This is particulat for the distinction between
  UIP and NSIP.
• With consistent clinical presentation and HRCT
  findings IPF can be diagnosed in 70 of the
  cases. For these cases surgical biopsy does not
  have an additional benefit. Surgical biopsy by
  itself is not significant without the clinical
  and radiological findings.
• Final diagnosis changed by 50 for the cases
  which lack the typical clinical and HRCT
  findings.

8
Idiopathic Interstitial Pneumonia What Is the
Effect of a Multidisciplinary Approach to
Diagnosis? Kevin R Flaherty Talmadge E King Jr
Ganesh Raghu Joseph P Lynch III et al American
Journal of Respiratory and Critical Care
Medicine Oct 15, 2004 170904-910

• 58 IIP cases diagnosed with surgical lung biopsy
  were investigated ina a stepwise manner
• Step 1 3 clinicians and 2 radiologists
  independently reviewed HRCT findings and recorded
  their individual diagnoses
• Step 2 3 standard clinical information and
  recorded their individual diagnoses
• Step 3 discussed HRCT findings with standard
  clinical information and recorded their
  individual diagnoses
• Patologhists (n 2) unaware of these information
  recorded their individual diagnosis
• Step 4 2 pathologists independently reviewed
  and discussed HRCT findings with standard
  clinical information and pathological findings
  and recorded their individual diagnoses
• Step 4 a consensus was sought, in case of
  disrepancy each recorded their individual
  diagnoses
• Agreement of the evaluations in these steps have
  been investigated

9
Idiopathic Interstitial Pneumonia What Is the
Effect of a Multidisciplinary Approach to
Diagnosis? Kevin R Flaherty Talmadge E King Jr
Ganesh Raghu Joseph P Lynch III et al American
Journal of Respiratory and Critical Care
Medicine Oct 15, 2004 170904-910

• Correct diagnosis as compared to pathologists
• Clinicians 17-27 less with only HRCT review,
  12-18 less with clinical infromation and
  radiologists discussion
• Radiologists 38-44 less with with only HRCT
  review , 34-41 less with clinical infromation
  and clinicians discussion Histopatolojik
  bilgiler
• After the histopathological information
  clinicians 3-12 better, radiologists 10-12
  better than the pathologists

Pathologist A Pathologist B Consensus
IPF 27 28 30
NSIP 11 14 15
RBILD/DIP 1 1 3
HP 2 1 1
BD 7 4 4
Diger 10 10 5
Correct diagnosis (reference pathologists C
clinical information, D discussion, P pathology
findings, Cs consensus,
10
Thomeer M, et al. Eur Respir J 200831585-591

• 36 investigators from 6 European countries
  examined 179 HRCT and 82 OLB/TBL. Local
  investiagators sent their speciamens to 2
  pathological investigation committee. Evaluations
  were classified as Very Suggestive, Probable
  and Unlikely.
  
  
  
• assessment of 512 HRCT
  
  
  
  -67 Unlikely (12.6),
  -203 Probable (38.2), - 258 Very Suggestive
  (48.5)
• assessment of 44 OLB, 38 TBL specimens
  
  
  
  - 76 Very Suggestive (42.7), - 66 Probable
  (37.1), - 33 Unlikely (18.5)
• UIP was diagnosed in 84 of the 82 biopsies,
  92.7 of the 165 HRCTs. When FVC (gt 60 or
  lt60) was added to HRCT review correct diagnosis
  increased to 100.
• Clinical diagnosis proportion 87.2
• Agreement was 0.40 in HRCT, and 0.30 in histology

11
Nicholson AG, et al. Thorax 200459500-505 Raghu
G, et al. Chest 19991161168-1174 Hanninghake
GW, et al. AJRCCM 2001164193-196 Ryu JH, et al.
Mayo Clin Proc 200782976-986

• In UK, 10 pathologists retrospectively examined
  133 lobar biopsy specimens of cases provided with
  age, sex and the biopsy site information, without
  findings of infection,.
• Confidence in the primary diagnosis of the
  pathologists was around 5. The agreement between
  the primary diagnosis of the pathologists was
  kappa 0.38, and increased to kappa 0.43 with
  confidence level gt70, when multiple biopsies
  were taken. For IPF agreement increased from
  kappa 0.42 to 0.49. Kappas were 0.76 to 0.82 for
  sarcoidosis , and 0.29 to 0.32 for NSIP,
  respectively. For UIP and NSIP, the differences
  between pathologists were significant in the end
  stage disease.
• According to these results, distinction in the
  histopathological diagnosis exists between
  routine pathological investigations.

12
Lettieri CJ, et al. Respiratory Medicine (2005)
99, 14251430
Histopathologicl Diagnosis Specialist Pathologist General Pathologist
Usual Interstitial Pneumonia 17 22
Non-Specific nterstitial Pneumonia 10 7
Sarcoidosis 4 0
Cryptogenic Organizing Pneumonia 3 3
Diffuse Alveoler Damage 2 1
Infecti on 2 1
Malignancy 2 0
other 5 10
Specialist Pathologists recorded distinct
diagnoss in 52.3, (kappa 0.21). This caused a
change in the treatment in 60. Sensitivity and
specificity of the general pathologists for IPF
were 76.5 and 66.7, respectively.
13
Visscher DW, Myers JL. Histologic spectrum of
idiopathic interstitial pneumonias. Proc Am
Thorac Soc 20063322

• Three major problems reaching a diagnosis of UIP,
  -The
  first is sampling, indeterminate pathologic
  findings,
  -Presence of
  fibrotic changes resembling UIP in other
  conditions,
  -Microscopic findings, that
  resemble other conditions.
• These problems need for clinical and radiographic
  correlation

14
This review is an attempt to address these
controversies and doing so provide the
pathologist with a straighforward and practical
approach to diagnosing the chronic interstitial
pneumoniast

Katzenstein ALA, et al. Human Pathology
2008391275-1294

• UIP Diagnostic Criteria
• 1. patchy involvement pattern of the
  parenchyma, non-uniform, distributed unevenly,
• 2. distorted structure, honey combing and scar,
• variable distribution of fibroblast foci
  and collagen deposition
  
• UIP can be mixed up with Asbestosis, HP, CVD,
  if the biopsy is taken from a single lobe small
  specimen could be consistent with NSIP. UIP has a
  heterogenous distribution.
  
  
• Hipersensitivite Pnomonisi can be mixed up with
  UIP. HP peribronchiolar epitheloid histiocyte
  non-nekrotising granuloma, mültinüclear giant
  cells, honey combing and fibrosis in advanced
  cases hardly distinguished from UIP.
• Since there is no entity like unclassified
  interstitial fibrosis, pathologists have
  difficulty in recording an appropriate diagnosis.
  This is especially the case for fibrotic NSIP.

15
Katzenstein ALA, et al. Diagnosis of usual
interstitial pneumonia and distinction from other
fibrosing interstitial lung disease. Human
Pathology 2008391275-1294

• Debate on the role of pathology in the diagnosis
  of IIP is one of the hot topics for the time
  being. More accurate and confirmed diagnoses are
  required for the consideration of novel,
  expensive treatments. Unclassified interstitial
  fibrosis cannot be offered as a diagnostic
  entity. This view could be inducing the
  pathologists to record an incorrect diagnosis.

16
Katzenstein ALA, et al. Human Pathology
2008391275-1294

• 4.1. How is honeycomb change defined
  microscopically, and what is its relationship, if
  any,
• to peribronchiolar metaplasia?
• 4.2. Because focal fibroblast proliferation is a
  feature of both fibroblast foci and BOOP, can
  they
• always be distinguished
• 4.3. Are fibroblast foci specific for UIP?
• 4.4. Because NSIP tends to occur in individuals
  slightly younger than those with UIP, and
  NSIP-like
• areas can be found in UIP, is NSIP an early form
  of UIP?
• 4.5. How much honeycomb change is too much to
  diagnose fibrosing NSIP?
• 4.6. How much interstitial inflammation can be
  present in UIP before another diagnosis
• is entertained?

17
Katzenstein ALA, et al. Human Pathology
2008391275-1294

• 4.7. When discordant biopsy results are
  encountered from different lobes, which is the
  correct diagnosis?
• 4.8. Because biopsies from one lobe may
  occasionally show NSIP in cases with otherwise
  typical UIP in other lobes, can NSIP be
  accurately diagnosed on a biopsy taken from a
  single lobe?
• 4.9. Once fibrosis becomes extensive, how
  important is it to separate fibrosing NSIP,
  chronic HP, and scarred LCH from UIP?
• 4.10. Can idiopathic interstitial pneumonias
  other than UIP be diagnosed on TBB?
• 4.11. If the experts do not always agree, can
  these diseases be accurately diagnosed?
• 4.12. Can ordinary (nonpulmonary) pathologists
  diagnose UIP and related idiopathic interstitial
  pneumonias?

18
Katzenstein ALA, et al. Human Pathology
2008391275-1294

• 4.13. By dividing interstitial lung disease into
  fibrotic predominant and cellular predominant
• variants, are we reverting back to the
  classification schemes of the 1970s and 1980s?
• 4.14. What terminology should be used on the
  pathology report when diagnosing the idiopathic
• interstitial pneumonias?

19
Fujita J, et al. Idiopathic non-specific
interstitial pneumonia as an autoimmune
interstitial pneumonia. Respir Med
200599234240. Selman M, et al. Gene
expression profiles distinguish idiopathic
pulmonary fibrosis from hypersensitivity
pneumonitis. Am J Respir Crit Care Med
2006173188198. Sahin H, et al. Chronic
hypersensitivity pneumonitis CT features
comparison with pathologic evidence of
fibrosis and survival. Ra Radiology
2007244591598.

• Investigations have revealed a predominant
  regulatory gene of extracellular matrix and
  chemokine activity regardless of the form of IIP
  as UIP or NSIP
• The slight difference between NSIP and UIP is
  surprizing for the clinical differences between
  IIPs. Others showed different transcript levels.
  The transcripts of familial IIP, which
  constitutes severe forms is different from
  sporadic IIPs.
• In IPF, immune cells other than macrophages, and
  dendritic cells are active. There is an
  association between pathological pulmonary
  fibrosis and inflammation.

20
IPF Tanisi Için Biyopsi Gerekmez

• Farkli loblardan alina biyopsi örnekleri
  birbirlerinden farkli histopatolojik örnekleri
  temsil edebilmektedir.
• Histopatolojik bulgular NSIP ve HP ile benzerlik
  gösterebilir.
• Histopatolojik UIP tanisi ile klinik tablo ve
  hastaligin dogal seyri, tedaviye yaniti her zaman
  paralellik göstermez.
• Biyopsi tanisi zamanla degisebilmektedir.
• UIPnin kesin tanisi için histopatolojik spesifik
  bir belirteç yoktur.
• Hastaligin dogal seyri, klinik belirti bulgulari,
  laboratuar sonuçlari, görüntüleme paternleri,
  tani yönünden histopatolojiye göre daha fazla
  yardimcidir.

21
IPF Pathogenesis

• Mutation in Telomerase Reverse Transcriptase
  (TERT) has been implicated for the pathogenesis.
• Stem/progenitor cell replace the injured and
  apoptotic cells in the tissue .
• Mesenchymal cells in the lung and alveolar type
  II cells express telomerase. This enzyme plays a
  critical role in the enhancement of the
  telomerase length.
• When the telomerase shortens the renewal capacity
  of the stem cell decreases and the cell gets aged
• Presence of mutant telomerase in the parenchymal
  cells could be responsible for the cellular death
  and/or limited regeneration capacity.
• Short telomerase phenotype could be found in IPF.
  
• However, telomerase length and telomerase action
  could be specific to the cell and autonomous

22
ILD (DPLD) Diagnosis

• History
  
  
  
  1-Natural history/chronology of
  the disease, -acute, chronic and episodic
  (Eosinophilic pneumonia, vasculitides, HP or COP)
  
  
  2-Respiratory risk factors and aetiological
  agents
  
  
  -Sigara -RB/ILD, DIP, LCH, Goodpasture synd.,
  IPF (odds ratio 1.6-2.9) HP and Sarcoidosis less
  likely
  -Occupation
  
  
  
  -Hobbies, Environment, Travel
  Antigens for HP, Eosinophilic lung disease
  
  -Family
  History -IPF, Sarcoidosis
  
  
  
  -HIV Risk Factors -Opportunistic
  infections, LIP
  
  
  - Rheumatological Symtoms
  
  
  
  -Past Medical Hystory Previous
  Malignancy, CT, RT, Surgery, -Vasculitis
  
  -Drug Hystory
  
  
  
  
  Symptoms
  
  
  
  -Cough, Sarcoidosis, HP, COP,
  IIPs,
• -Wheezing, Eosinophilic pneumonia,
  Churg-Strauss syndrome,
• -Pleural Inflamation, CVDs, Asbestos
  exposure,Drugs,
• Physical Examination
• -Digital Clubbing, IPF, HP, CVD/ILD
• -Crackles (velcro) IPF, HP,
  Sarcoidosis
• -Inspiratory Squeaks, HP, NSIP,
• -Disease severity and cardiopulmonary
  capacity
• -Extrapulmonary Signs

23
DPLD (ILD) Siniflandirmasi

• Known Cause
  
  
  -Hypersensitivity
  pneumonitis,
  
  
  -Connective Tissue Diseases associated ILDs,
  
  
  -Drug-induced ILDs,
  
  
  -Smoking-related ILDs
• Pulmonary Langerhans cell
  histiocytosis?,
• Respiratory bronchiolitis-associated
  ILD? (RB-ILD),
• Desquamative interstitial pneumonia?
  (DIP),
• Acute eosinophilic pneumonia,
  
  
  -Radiation-induced ILDs,
  
  
  
  -Toxic inhalation-induced ILDs
• Unknown Cause
• Idiopathic Interstitial Pneumonias
  
  
• -Idiopathic pulmonary fibrosis
• -Non-Specific interstitial
  pneumonia
• -Acute interstitial pneumonia
• -Lymphocytic interstitial
  pneumonia
• -RB-ILD,
• -DIP,
• -Cryptogenic organizing
  pneumonia
• Eosinophilic Pneumonias
• Pulmonary Lymphangioleiomyomatosis

24
ILD Klinik Karakteristikleri

• ÖYKÜ
  
  
  
  1-Hastaligin dogal ve kronolojik seyri akut,
  -kronik, -epizodik (Eozinofilik pnomoni,
  -vaskülit/pulmoner hemoraji, -HP, -COP
  
  
  
  2-Risk Faktörleri, Etyolojik Nedenler
  
  
  -Sigara RB-ILD, DIP, LCH,
  Goodpasture Send., IPF(odds ratio 1.6-2.9) -HP ve
  Sarkoidozis zayif olasilik,
  -Meslek,
  
  
  
  -Hobiler/çevre/seyahat -HP antijeni, Eozinofilik
  hastalik
  
  
  -Aile Hikayesi IPF ve Sarkoidozis,
  
  
  -HIV Risk Faktörü,
  -Opurtunistik infeksiyon , LIP,
  
  
  -Romatolojik Belirtiler,
  
  
  
  -Önceki Tibbi Öykü, -Malignite, KT, RT, Cerrahi
  girisim, Vaskülit/Hemoraji,
  -Ilaç
  Tedavileri,
• BELIRTILER
  
  
  -Öksürük,
  -Sarkoidozis, HP, COP, IIPler,
  
  
  -Hisiltili gtSoluk, -Eozinofilik
  pnomoni, Churg Strauss sendromu,
  
  -Hemotezi, -Wegeners
  granülomatozu, Goodpasture send.
  
  -Plörezi, -KVHlar,
  Asbestoz temasi, Ilaçlar,
  
  
• FIZIK MUAYENE
  
  
  -Çomak parmak,
  -IPF, RK.HP, KVH/ILD,
  
  
  -Velcro benzeri crackles, -IPf, HP,
  Sarkoidozis,
  
  -Inspiratuar
  Squeaks, -HP, NSIP,
  
  
  
  -Hastaligin Siddeti, Efor kapasitesi,
  
  
  -Solunum Fonksiyonlari,
  Genelde restriktif bozukluk, Küçük hava yollari
  için FEF25-75 , FEF75,, FEF85 ve
  FVC ( FVC lt 60 ileri evre), Tlco lt
  40 ileri evre hastalik
  
  
  
  

25
Shigeki Misumi and David A. Lynch Idiopathic
Pulmonary Fibrosis/Usual Interstitial Pneumonia
Imaging Diagnosis, Spectrum of Abnormalities, and
Temporal Progression Proc Am Thorac Soc
20063307314

• Features Helpful in CT Diagnosis of Fibrotic Lung
  Diseases
• ______________________________UIP______DIP_____NSI
  P____Kr_HP_____
• Subpleural predominance
  0
  
• Peribronchovascular predominance 0
  0 0
  
• Ground glass
  0
  
• Reticular
  0 0 0
  0
• Honeycombing
  0 0
  0
• Nodules
  0 0 0
  
• Mosaic attenuation/air trapping 0
  0 0
  
• Cysts
  0 0
  0
• 0 feature is not helpful in the CT diagnosis,
  feature is very importante CT Diag.

26
Shigeki Misumi and David A. Lynch Idiopathic
Pulmonary Fibrosis/Usual Interstitial Pneumonia
Imaging Diagnosis, Spectrum of Abnormalities, and
Temporal Progression Proc Am Thorac Soc
20063307314

• Prevalance of Imaging Features in Fibrotic Lung
  Diseases
• __________________________________UIP_______DIP___
  ___NSIP_____Kr_HP____
• Subpleural predominance
  0
  
• Peribronchovascular predominance 0
  0
  0
• Ground glass
  
  
• Reticular
  
  
• Honeycombing
  
  
• Nodules
  0 0
  0
• Mosaic attenuation/air trapping
  0 0 0
  
• Cysts
  0
  0 0
• 0 feature does not occur, feature
  is present in all or almost all cases

27
Ryu JH, et al. Diagnosis of Interstitial Lung
DiseasesMayo Clin Proc 2007 82976-986

• Diagnosis of Interstitial Lung Diseases
• Radyolojik Bulgular
• Konsolidasyon
• Akut DAH, AIP, Akut Eoz.Pnomoni, COP,
  Ilaçlarla ILD,
• Kronik Kr. Eoz.Pnom. COP, PAP, Sarcoidosis,
  Lenfoma
• Retiküler Patern
• Akut Pulm. Ödem
• Kronik IPF, HP, Asbestozis, Sarkoidozis,
  Ilaçlarla ILD
• Nodüler Patern lt1cm / çap
• Akut HP, Sarkoidozis, Infeksiyon
• Kronik Sarkoidozis, HP, Resp.
  Bronsiyolitis, Alveolar Mikrolitiyazis.
• Kistik
• Akut Pnomosistitis pnomonisi, Septik
  embolizm
• Kronik LCH, LAM, Lenfositik interstisyel
  pnomoni, Bal petegi-IPF
• Buzlu Cam Opasiteleri
• Akut DAH, HP, AIP, Ilaçlara bagli ILD,
• Kronik NSIP, HP, Resp. Bronsiyolitis ve
  ILD, DIP, PAP, Ilaçlara bagli ILD

28
ILD (DPLD) Tanisi

• Pulmonary Function Tests
• -Spirometry, Diffusion capacity,
  oximetry,
• - Arterial blood gas and pH
• -Cardiopulmonary exercise test,
• Laboratory Tests
• -Complete blood cell count
• -Chemistry panel,
• -Serologic tests fo HP,
• -Tests for CVD,
• -Antineutrophil cytoplasmic
  antibodies,
• -BNP, proBNP,
• Imaging Studies
• -CXR,
• -Previous imaging studies,
• -Chest CT and HRCT
• Bronchoscopy

29
Ryu JH, et al. Diagnosis of Interstitial Lung
DiseasesMayo Clin Proc 2007 82976-986

• Thickened Interlobular Septa
• -Acute Congestive heart failure,
  Pulmonary edema,
• -Chronic Sarkoidosis, PAP
•  Associated Findings
• Traction Bronchiectasis IPF, Asbestosis,
  Other chr. Fibrotic disorders,
• Lymphadenopathy Sarkoidosis, Berilliosis,
  Infections, Lymphangitis cars. Lymphoma,
• Air Trapping HP, Resp. Bronchiolitis
  associated ILD, DIP, Sarkoidosis,
• Pleural Effusion or Thickening Asbestosis,
  KVH-ILD, LAM, Lymphoma, Lymnfangitic
  carcinomatosis, drug-induced ILD
• ILDnin bilinen histopatolojik patern sayisi
  sinirlidir. Bu paternlerin tanisal özellikleri
  farklidir. Bazi biyopsi spesmenler tanisal
  özellikler tasirken bazilari nonspesifik
  anormallikler gösterir.

30
Ryu JH, et al. Diagnosis of Interstitial Lung
DiseasesMayo Clin Proc 2007 82976-986

• Interlobüler Septal Kalinlasma
• -Akut Kalp yetmezligi, Pulmoner ödem,
• -Kronik Sarkoidozis, PAP
•  Diger Bulgular
• Traksiyon Bronsiyektazisi IPF, Asbestozis,
  Diger kr. Fibrotik bozukluklar,
• Lenfadenomegali Sarkoidozis, Berilyozis,
  Silikozis, Infeksiyon, Lenfanjitis kars. Lenfoma,
  
• Air Trapping HP, Resp. Bronsiyolitis ve ILD,
  DIP, Sarkoidozis,
• Plevral Sivi veya Kalinlasma Asbestozis,
  KVH-ILD, LAM, Lenfoma, Lenfanjitis, Ilaca bagli
  ILD
• ILDnin bilinen histopatolojik patern sayisi
  sinirlidir. Bu paternlerin tanisal özellikleri
  farklidir. Bazi biyopsi spesmenler tanisal
  özellikler tasirken bazilari nonspesifik
  anormallikler gösterir.

31
Ryu JH, et al. Diagnosis of Interstitial Lung
DiseasesMayo Clin Proc 2007 82976-986

• Diagnosis of Interstitial Lung Diseases
• Radiologic Findings
• Consolidation
• Acute DAH, AIP, Acute Eos.Pneumonia, COP,
  Drug-induced ILD,
• Chronic Chr. Eos.Pneum. COP, PAP,
  Sarcoidosis, Lymphoma
• Reticular Pattern
• Acute Pulm. Odema,
• Chronic IPF, CVD/ILD, Asbestosis,
  Sarcoidosis, HP, Ilaca bagli ILD,
• Cystic Airspace
• Acute Pneumocystis pneumonia, Septic
  embolism
• Chronic LCH, LAM, LIP, IPF-honeycomb lung
• Ground-glass Opacities
• Acute DAH, HP, AIP, Drug-induced ILD,
• Chronic NSIP, HP, Resp. Bronchiolitis
  associated ILD, DIP, PAP, Drug induced ILD

32
Lleslie KO. Clin Chest Med200425657-703,
Verbeken EK. Eur Respir J 200132Suppl.107S-113S

•  
• Diger Bulgular
• Traksiyon Bronsiyektazisi IPF, Asbestozis,
  Diger kr. Fibrotik bozukluklar,
• Lenfadenomegali Sarkoidozis, Berilyozis,
  Silikozis, Infeksiyon, Lenfanjitis kars. Lenfoma,
  
• Air Trapping HP, Resp. Bronsiyolitis ve ILD,
  DIP, Sarkoidozis,
• Plevral Sivi veya Kalinlasma
  AsbestozisILDnin bilinen histopatolojik patern
  sayisi sinirlidir. Bu paternlerin tanisal
  özellikleri farklidir. Bazi biyopsi spesmenler
  tanisal özellikler tasirken bazilari nonspesifik
  anormallikler gösterir.
• , KVH-ILD, LAM, Lenfoma, Lenfanjitis, Ilaca bagli
  ILD

33
Athol U. Wells1 and Cory M. Hogaboam. Update in
Diffuse Parenchymal Lung Disease 2007 Am J Respir
Crit Care Med 2008Vol 177. pp 580584,

• NSIP initially was regarded as a confusing
  preliminary diagnosis and a presentation. It was
  classified as idiopathic NSIP and HP, and NSIP
  secondary to drug induced lung disease and
  especially to CVD
• Recent information suggest that this distinction
  is not valid. When idiopathic NSIP is
  investigated precisely it is revealed that the
  clinical and serological abnormalities are due to
  the underlying CVD or its development, which did
  was not noticed. Another supporting evidence is
  the similarity of the survival between idiopathic
  NSIP and NSIP secondary to CVD. In contrast to
  that mortality in IPF is higher than that
  associated with CVD and UIP.
• The classification has to be updated according to
  these views. The previous classification carries
  difficulties for the invesigations of new
  treatments. Fibrotic NSIP develops in HP, and is
  also a subgroup of idiopathic NSIP related to HP.
  The prognostic value of this pattern of HP is not
  well known, however recent data suggests that
  widespread reticular findings with or without
  honey combing and traction bronchiectasis in the
  CT illustrates the presence of fibrotic disease.

34
Athol U. Wells1 and Cory M. Hogaboam. Update in
Diffuse Parenchymal Lung Disease 2007 Am J Respir
Crit Care Med 2008Vol 177. pp 580584,

• NSIP baslangiçta bir ön tani ve tani kargasasi
  yaratan tablo seklindeydi. Idyopatik NSIP ve HP,
  Ilaca bagli akciger hastaligi ve özellikle
  KVHlara sekonder NSIP olarak siniflandirilmaktayd
  i.
• Son bilgiler bu ayrimin yapay oldugunu
  düsündürmektedir. Idyopatik NSIP dikkatli
  arastirildiginda klinik ve serolojik
  anormalliklerin kuvvetle altta ayrimi yapilmamis
  KVHligi veya ona dogru gidisi düsündürdügü
  görülmektedir. Bunu destekleyen bir durum,
  idyopatik NSIPle KVHlara segonder NSIP
  survivallari benzerdir. Zit olarak IPFde
  mortalite, KVH ve UIP birlikte bulunanlardan daha
  yüksektir.
• Bu görüslerle yeniden siniflandirmalidir. Eski
  siniflandirma yeni tedavi arastirmalari için
  zorluklar tasimaktadir. HPde fibrotik NSIP ve
  UIP gelisir, ve gene çalismalari HPin altinda
  idyopatik NSIPin bir alt grubudur. HPdeki bu
  paternin göreceli prognostik degeri
  bilinmemektedir, ancak son raporlara göre BTdeki
  yaygin retiküler bulgular bal petegi ve traksiyon
  bronsiyektazisi olsun olmasin altta bulunan
  fibrotik hastaligi göstermektedir.